M= Mouse; R=Rat; H=Human; Rb=Rabbit; G=goat; B=Bovine, MO=Monkey; P=pig; CT= near C-terminus; NT=near N-terminus; Internal=Middle of protein. EC=extracellular; CP=cytoplasmic domains *

 

Anti-Oxidant Enzymes: Superoxide Dismutases (SOD1, SOD2, SOD3), Cu-Chaperone protein for SOD (CCS), Glutathione Peroxidase and Catalase -General Information

Highly reactive and potentially dangerous reactive oxygen species (ROS) are normally produced within the cells, primarily from the mitochondrial respiratory chain where in excess electrons are donated to molecular oxygen (o2) to generate peroxide anion (O2-). Superoxide anion is reduced by the superoxide dismutase (SOD) to hydrogen peroxide (H2O2) and hydrogen peroxide is reduced to water (H2O) by catalase, located primarily in the peroxisomes, and by glutathione peroxidase (GPx), located in the mitochondria and cytosol. Hydrogen peroxide, in the presence of transitions metals, can be converted to the highly toxic hydroxyl radical (OH.) and all three of the ROS (O2-, H2O2, and OH.) can damage macromolecules (proteins, DNA etc). The GPxs are commonly considered the most important for ROS defense since they have broader substrate specificities and stronger affinity for H2O2 than catalases.

Superoxide dismutase (SOD) is an enzyme, which thought to play a role in the protection of aerobic cells against oxygen toxicity by catalyzing disputation of superoxide anion (O2-) to H2O2 and O2. SODs are found in 3 forms and produced by separate genes. The first isoforms (SOD1, also known as SOD-A, soluble SOD, Cytosolic SOD, Cu-Zn SOD and indophenoloxidase A or IPOA). Human SOD1 is 154 aa (chromosome 21q22). It is a homodimer and each subunit can bind 1 copper ion and 1 zinc ion. SOD1 is cytoplasmic protein. Defects in SOD1 are the cause of familial amyotrophic lateral sclerosis (FALS) or amyotrophic lateral sclerosis 1 (ALS1 or ALS). ALS is a degenerative disorder of motorneurons in the cortex, brainstem and spinal cord. ALS is characterized by muscular weakness and atrophy beginning in the hands and spreading to the forearms and legs. Death usually occurs within 2 to 5 years. The familial form of ALS accounts for about 10% of the cases and is transmitted in an autosomal dominant manner.

SOD2 (mitochondrial indophenoloxidaeB, IPO-B, Mn-SOD) is a Mn-containing enzyme found primarily in mitochondria and therefore is not present in erythrocytes. SOD2 (human 222-aa; chromosome 6q25.3) is a homotetramer. It binds 1 Mn per subunit. SOD3 (extracellular-SOD or EC-SOD) is found in extracellular space (blood, lymph, synovial fluids and cerebrospinal fluid). Human SOD3 (240-aa, signal peptide 1-18aa; chromosome 4p15.3-p15.1) is a homotetramer. Each subunit, 30 kda, can bind 1 Cu and 1 Zn. Approx. 99% of EC-SOD is anchored to heparan sulfate proteoglycans in the tissue interstitium, and 1% is located in the vasculature in equilibrium between the plasma and the endothelium.

Copper (Cu) is an essential metal that is required for normal physiological activities. It is also highly toxic. Therefore. It must be transported in non-reactive forms as it moves through the cellular compartments. The metallochaperone protein would deliver the Cu to acceptor protein such as Cu-Zn superoxide dismutase (SOD). The human Cu-Chaperone protein for SOD (CCS) is a homolog of yeast protein Lys7. CCS (human 274-aa, chromosome 11q13) is 47% identical with SOD1. The metal binding regions are more conserved between CCS and SOD1. CCS and SOD1 are distributed in an identical pattern throughout the cytoplasm and nucleus of mammalian cells

Two of the main types of glutathione peroxidases (GPxs) that have been characterized in cells are the classical GPx (cGPx) and the phospholipid hydroperoxide GPx (PHGPx). cGPx is multimeric (commonly tetrameric) and soluble, whereas PHGPx is monomeric and often membrane-associated. In addition, whereas cGPx has specificity for glutathione as a reducing substrate, PHGPx re-reduction may be coupled to alternative systems such as the thioredoxin pathway . Thus, PHGPx is often considered the principal cellular enzyme capable of repairing membrane lipid peroxidation, the highly damaging process that has been linked to pathological conditions such as ischemic injury, atherosclerosis, and carcinogenesis. Human GPX1 (Glutathione peroxidase 1 or GSHPx-1 or Cellular glutathione peroxidase, 201-aa, chromosome 3p21.3) contains Selenium in the form of selenocysteine. GPX is one of only a few proteins known in higher vertebrates to contain selenocysteine. This unusual amino acid occurs at the active site of GPX and is coded by the nonsense (stop) scodon TGA. Neonatal deficiency of the selenoenzyme glutathione peroxidase, with hematologic consequences, may result from 'selenium imbalance' during pregnancy.

Catalase (CATA, 527 aa, chromosome 11p13) is peroxisomal enzyme found in almost all aerobically respiring organisms and serves to protect cells from the toxic effects of hydrogen peroxide. It is homotetramer. Defects in CAT are the cause of acatalasia or acatalasemia. This disease is characterized by absence of catalase activity in red cells and is often associated with ulcerating oral lesions.

All Products are for in vitro research use only.